Direct sub-second measurement of neuromodulator signaling during risky decision-making

项目摘要 决策神经科学的许多工作都是基于这样一种假设，即多巴胺能信号在决策神经系统中起着重要的作用。 在价值表征及其更新中起着关键作用，最近的工作将这种异常联系起来， 对精神疾病的特定特征的价值表征（例如，重度抑郁症中的快感缺乏）。然而，在这方面， 尽管风险在评估选择方案中起着重要作用， 在精神疾病中发挥作用，包括极端的焦虑症和物质等健康风险行为， 在另一方面，对风险的神经生物学的理解仍然难以捉摸。间接证据来自 药理学研究表明，肾上腺素能和去甲肾上腺素能信号传导都可能在 然而，直接测量5-羟色胺或去甲肾上腺素信号， 选择还有待于在人类身上进行检验。 MPI Montague小组的最新进展使得前所未有的追踪神经调质的能力成为可能。 具有高时间分辨率和化学特异性的响应。具体来说，MPI Montague的团队能够 直接和同时测量多巴胺和5-羟色胺的反应，在清醒的人与颞 检查神经调质释放与决策的关系所需的分辨率（~ 1 ms） 流程.对于信号识别和提取，记录方法使用机器学习算法 （弹性网络回归）结合电化学，仅使用现成的硬件和软件。的 这种“弹性网络电化学”的产物是亚秒级的体内神经调质波动的记录 分辨率该应用程序将MPI King-Casas的决策神经科学专业知识与这些 MPI Montague直接检查肾上腺素能、去甲肾上腺素能和多巴胺能功能的进展 在冒险的选择。 为了实现这一目标，我们将记录耐药的参与者的神经调质反应。 已经有颅内深部电极用于II期监测的癫痫患者。深部电极将 由我们弗吉尼亚理工大学医学附属机构Carnival Clinic（Carnival Clinic）的神经外科同事植入 PI：巫师）。在记录过程中，参与者将执行i）风险诱发任务（Holt & Laury类型任务）和ii） 奖励学习任务（多臂强盗任务）已经被我们的团队和其他人证明是可靠的， 唤起与风险和表征相关的神经反应，因为它们在标准中被监测（即， 非手术）医院套间。深度记录将使用包括多个 沿着内侧前额叶皮质的背侧-喙侧轴接触。

PROJECT SUMMARY Much work in decision neuroscience has been predicated on the hypothesis that dopaminergic signaling plays a critical role in value representations and their updating, and recent work has linked abnormalities in such value representations to specific features of psychiatric illness (e.g., anhedonia in major depression). However, despite the fundamental role that risk plays in evaluating choice options as well as the role sensitivity to risk plays in psychiatric illness, including anxiety disorders at one extreme and health risk behaviors like substance use at another other, an understanding of the neurobiology of risk remains elusive. Indirect evidence from pharmacological studies have suggested both serotoninergic and noradrengergic signaling may play roles in representations of risk; however, direct measurement of serotonin or norepinephrine signaling during risky choice has yet to be examined in humans. Recent advances by MPI Montague’s group allow the unprecedented ability to track neuromodulator responses with high temporal resolution and chemical specificity. Specifically, MPI Montague’s team is able to directly and simultaneously measure dopamine and serotonin responses in awake humans with the temporal resolution (~ 1 ms) required to examine the relationship of neuromodulator release with decision-making processes. For signal identification and extraction, the recording method uses machine-learning algorithms (elastic net regression) combined with electrochemistry using only off-the shelf hardware and software. The product of this ‘elastic net electrochemistry’ is recordings of in vivo neuromodulator fluctuations at sub-second resolution. This application merges the decision neuroscience expertise of MPI King-Casas with these advances of MPI Montague to directly examine serotonergic, noradrenergic, and dopaminergic functioning during risky choice. To achieve this goal, we will record neuromodulator responses in participants with medication-resistant epilepsy who already have intracranial depth electrodes in place for phase-II monitoring. Depth electrodes will be implanted by our neurosurgery colleagues at Virginia Tech’s medical affiliate Carilion Clinic (Carilion Clinic PI: Witcher). During recording, participants will perform i) a risk elicitation task (Holt & Laury type task) and ii) a reward learning task (multi-arm bandit task) that have been shown by our group and others both to reliably evoke neural responses associated with risk and representations as they are monitored in a standard (i.e., non-surgical) hospital suite. Depth recordings will be made using a standard montage that includes multiple contacts along the dorsal-rostral axis of the medial prefrontal cortex.